rs193302850
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The ENST00000204679.9(GNPTG):c.379_391del(p.Asp127ProfsTer31) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,611,484 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as not provided (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
GNPTG
ENST00000204679.9 frameshift
ENST00000204679.9 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.26
Genes affected
GNPTG (HGNC:23026): (N-acetylglucosamine-1-phosphate transferase subunit gamma) This gene encodes the gamma sunbunit of the N-acetylglucosamine-1-phosphotransferase complex. This hexameric complex, composed of alpha, beta and gamma subunits, catalyzes the first step in synthesis of a mannose 6-phosphate lysosomal recognition marker. This enzyme complex is necessary for targeting of lysosomal hydrolases to the lysosome. Mutations in the gene encoding the gamma subunit have been associated with mucolipidosis IIIC, also known as mucolipidosis III gamma.[provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| GNPTG | NM_032520.5 | c.379_391del | p.Asp127ProfsTer31 | frameshift_variant | 6/11 | ENST00000204679.9 | NP_115909.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| GNPTG | ENST00000204679.9 | c.379_391del | p.Asp127ProfsTer31 | frameshift_variant | 6/11 | 1 | NM_032520.5 | ENSP00000204679 | P1 |
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152256Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000205 AC: 5AN: 243906Hom.: 0 AF XY: 0.00000752 AC XY: 1AN XY: 133000
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GnomAD4 exome AF: 0.00000548 AC: 8AN: 1459228Hom.: 0 AF XY: 0.00000551 AC XY: 4AN XY: 725908
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GnomAD4 genome 0.0000131 AC: 2AN: 152256Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74380
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ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
GNPTG-mucolipidosis Other:1
| not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at